NIR-excited imaging of drug-induced liver injury using a superoxide-activated ratiometric upconversion luminescence nanoprobe.

ABSTRACT

Drug-induced liver injury (DILI) poses a significant risk to human health. Increasing evidence indicates that the superoxide anion (O2•-), as the precursor of the other reactive oxygen species, is key in the pathological processes associated with DILI. Nonetheless, understanding of the mechanisms of DILI is difficult due to the lack of an imaging tool for monitoring the fluctuation of O2•- levels during the progression of DILI. Herein, we developed an upconversion nanoprobe (Rbh-UCNs) for in vivo ratiometric tracking of endogenous O2•- in DILI. In this design, the addition of O2•- triggers the luminescent resonance energy transfer between Rbh and UCNs, which significantly enhances absorption centered at 534 nm and translates into a distinct decrease of the UCL emission at 543 nm, while the UCL emission peak at 654 nm and 800 nm are not significantly affected, offering a ratiometric UCL signal for the quantitative detection of O2•-. In addition, Rbh-UCNs could effectively visualize endogenous O2•- in living cells, zebrafish, and liver tissues upon stimulation with PMA or cisplatin. More importantly, tissue imaging of the liver region of mice revealed that the fluctuation of O2•- levels is associated with DILI and the protective effect of L-carnitine against DILI. Altogether, this study provides an available method for a deeper comprehension of the mechanisms underlying DILI and accelerating the development process of hepatoprotective medicines.